Ethanol → 9-(5-Cyclopropyl-1H-pyrazol-3-yl)-N-[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]-9H-purin-2-amine

HRID 450398Notes

Reaction equation

HRID 450398 reaction equation
[CH:1]1([C:4]2[NH:8][N:7]=[C:6]([NH:9][C:10]3[C:15]([N+:16]([O-])=O)=[CH:14][N:13]=[C:12]([NH:19][C@H:20]([C:22]4[N:27]=[CH:26][C:25]([F:28])=[CH:24][N:23]=4)[CH3:21])[N:11]=3)[CH:5]=2)[CH2:3][CH2:2]1.[CH2:29](O)C.C(O)(=O)C.C(N)=N.C(OCC)(=O)C>[Cl-].[Na+].O.[Pd]>[CH:1]1([C:4]2[NH:8][N:7]=[C:6]([N:9]3[CH:29]=[N:16][C:15]4[C:10]3=[N:11][C:12]([NH:19][C@H:20]([C:22]3[N:27]=[CH:26][C:25]([F:28])=[CH:24][N:23]=3)[CH3:21])=[N:13][CH:14]=4)[CH:5]=2)[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 702EthanolHCID 8857Ethyl AcetateHCID 160693Formamidine acetateHCID 686069435-Nitro-N4-(5-cyclopropyl-1H-pyrazol-3-yl)-N2-[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]pyrimidine-2,4-diamine2×

Product 1

HCID 251159659-(5-Cyclopropyl-1H-pyrazol-3-yl)-N-[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]-9H-purin-2-amine

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 57417360Sodium chloride; waterSolvent

Procedure

N4-(5-cyclopropyl-1H-pyrazol-3-yl)-N2-[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]-5-nitropyrimidine-2,4-diamine (Intermediate 18, 0.25 g) was dissolved into ethanol (20 mL) with Pd—C (40 mg) and a hydrogen inlet. The mixture was stirred at room temperature until no starting material was detected with TLC or LCMS. Formamidine acetate (0.5 g) was added to the filtrate after the filtration of resulting mixture. The mixture was stirred at 95° C. for 4 hours. Ethyl acetate (40 mL) was added into the resulting mixture, and brine (10 mL×3) was used to wash the organic layer. The organic layer was dried and concentrated. The resulting residue was separated by silica gel column (Ethyl acetate/MeOH) to afford 0.013 g of the title compound. MS (electrospray): 366 (M+1) for C17H17FN9. 1H NMR (300 MHz, CD3OD) δ ppm 8.70 (s, 2H) 8.65 (s, 1H) 8.40 (s, 1H) 6.40 (d, 1H) 5.30 (dd, 1H) 2.00 (m, 1H) 1.65 (d, 3H) 1.10 (m, 2H) 0.90 (m, 2H).

Workup

  1. filtrationafter the filtration
  2. customof resulting mixture
  3. stirringThe mixture was stirred at 95° C. for 4 hours
  4. washto wash the organic layer
  5. customThe organic layer was dried
  6. concentrationconcentrated
  7. customThe resulting residue was separated by silica gel column (Ethyl acetate/MeOH)

Sources & evidence

ORD record
ord-bf3121626ca44168801a07f1d909c3e8
Source dataset
uspto-grants-2013_07
Patent number
US08486966B2

Reaction notes

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